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P-glycoprotein transporter expression on a549 respiratory epithelial cells is positively correlated with intracellular dexamethasone levels.
MedLine Citation:
PMID:  20940624     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
BACKGROUND: Several mechanisms of glucocorticoid resistance in asthma have been proposed. P-glycoprotein (P-gp), a ubiquitous efflux transport protein, is associated with variability in the disposition of many drugs and interindividual variability in drug treatment response. This study was undertaken to determine the effect of P-gp expression on glucocorticoid efflux from airway epithelial cells.
HYPOTHESIS: Decreasing respiratory epithelial P-gp expression in dexamethasone-exposed airway epithelial cells in vitro will increase intracellular dexamethasone concentration.
METHODS: A549 lung epithelial cells, transfected with small interfering RNA (siRNA) targeted at messenger RNA for the gene encoding P-gp, were exposed to 100-nM dexamethasone for 15 minutes. Transfection efficiency of siRNA, P-gp expression, and intracellular dexamethasone were measured with flow cytometry.
RESULTS: Cells transfected with both negative siRNA and siRNA targeted at P-gp exhibited a positive correlation of P-gp expression with intracellular dexamethasone. The mean ± SEM correlation coefficients were 0.78 ± 0.07 for cells transfected with negative siRNA and 0.79 ± 0.08 for cells transfected with siRNA targeted at P-gp.
DISCUSSION: Contrary to our hypothesis, the positive correlation between P-gp expression and intracellular dexamethasone suggests that P-gp is not a primary transporter of glucocorticoids from airway epithelial cells. Increased P-gp expression is unlikely to be an important mechanism of glucocorticoid resistance in asthma.
Authors:
Joanna S Cohen; Angela S Benton; Fisayo Nwachukwu; Tugba Ozedirne; Stephen J Teach; Robert J Freishtat
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of investigative medicine : the official publication of the American Federation for Clinical Research     Volume:  58     ISSN:  1708-8267     ISO Abbreviation:  J. Investig. Med.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9501229     Medline TA:  J Investig Med     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  991-4     Citation Subset:  IM    
Affiliation:
Center for Genetic Medicine Research, Children's National Medical Center, 111 Michigan Ave. NW, Washington, DC 20010, USA. jcohen@cnmc.org
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